Dissolution testing compendial

The Joint Panel proposed no in vivo requirements, but individual dissolution testing requirements were adopted in 12 compendial monographs. USP tests measured the time to attain a specified amount dissolved, whereas NF used the more workable test for the amount dissolved at a specified time. Controversy with respect to equipment selection and methodology raged at the time of the first official dissolution tests. As more laboratories entered the field, and experience (and mistakes ) accumulated, the period 1970-1980 was one of intensive refinement of official test methods and dissolution test equipment. 

The USP Dissolution General Chapter < 711 > describes the basket (Apparatus 1) and paddle (Apparatus 2) in detail. There are certain variations in usage of the apparatus that occur in the industry and are allowed with proper validation. The literature contains a recommendation for a new USP general chapter for dissolution testing (6). In this article, guidance for method validation and selection of equipment is described. It may be a useful guide when showing equipment equivalence to compendial equipment. 

Compendial Requirements of Dissolution Testing—European Pharmacopoeia, Japanese Pharmacopoeia, United States... 

INTRODUCTION AND IMPLEMENTATION OF COMPENDIAL DISSOLUTION TEST REQUIREMENTS... 

Several in vitro tests are currently employed to assure drug product quality. These include purity, potency, assay, content uniformity, and dissolution specifications. For a pharmaceutical product to be consistently effective, it must meet all of its quality test criteria. When used as a QC test, the in vitro dissolution test provides information for marketing authorization. The dissolution test forms the basis for setting specifications (test, methodology, acceptance criteria) to allow batch release into the market place. Dissolution tests also provides a useful check on a number of physical characteristics, including particle size distribution, crystal form, etc., which may be influenced by the manufacturing procedure. In vitro dissolution tests and QC specifications should be based on the in vitro performance of the test batches used in in vivo studies or on suitable compendial specifications. For conventional-release products, a single-point dissolution... 

Various dissolution test systems have been developed and several of them now enjoy compendial status in pharmacopeias, for example the reciprocating cylinder (United States Pharmacopeia Apparatus 3), the flow-through apparatus [European Pharmacopoeia (Pharm. Eur.) 2.9.3], or the apparatus for transdermal delivery systems, such as the paddle over disc. Hydrodynamic properties of these and other apparatus have been described only sparingly. The paucity of quantitative data related to hydrodynamics of pharmacopeial dissolution testers is lamentable, since well-controllable hydrodynamics are essential to both biopharmaceutical simulations and quality control. Here, we focus the discussion on the paddle and the basket apparatus, since these are the most important and widely used for oral solid dosage forms. A brief treatise on the hydrodynamics of the flow-through apparatus completes this section. 

For the dissolution test to be used as an effective drug product characterization and quality control tool, the method must be developed with the various end uses in mind. In some cases, the method used in the early phase of product and formulation development could be different from the final test procedure utilized for control of the product quality. Methods used for formulation screening or BA and/or bioequivalency evaluations may simply be impractical for a quality control environment. It is essential that with the accumulation of experience, the early method be critically re-evaluated and potentially simplified, giving preference to compendial apparatus and media. Hence, the final dissolution method submitted for product registration may not necessarily closely imitate the in vivo environment but should still test the key performance indicators of the formulation. 

Rotational Speed. The rotational speed of a basket or paddle is an important consideration in the development and validation of the dissolution test. A speed of 100 rpm is commonly used with the basket apparatus and a speed of 50 rpm is used with paddles. In method validation, one needs to ensure that slight variations in rotational speed will not affect the outcome of the dissolution test. The compendial limit for variations in rotational speed is 4%, but a wider variation (e.g., 10%) may be considered in testing the robustness of the method. 

All modified release solid oral dosage forms In the presence of an established in vitro/in vivo correlation (6), only application/compendial dissolution testing need be performed (i.e., only in vitro release data by the correlating method... 

In the presence of an established in vitro/in vivo correlation only application/ compendial dissolution testing should be performed. 

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